Luo Zhou, Yuze Cao, H. Long, Lili Long, Lin Xu, Zhaoqian Liu, Ying Zhang, B. Xiao
Drug resistance is common in epilepsy despite multiple available medications. Single nucleotide polymorphisms (SNP) may influence drug efficacy in epilepsy. We therefore aimed to clarify the association between polymorphisms of several controversial SNP loci and drug resistance in Chinese Han epilepsy patients from central China. Among all the 391 recruited subjects, 235 and 156 patients were classified into a drug responsive and resistant group, respectively, according to the definition of drug resistance proposed by the International League Against Epilepsy. The candidate SNP loci, including ATP-binding cassette (ABC) subfamily gene ABCB1 rs2032582 and rs1045642; ABC subfamily gene ABCC2 rs717620 and rs2273697; sodium channel subunit gene SCN1A rs3812718, SCN2A rs2304016; γ-amino butyric acid type A (GABAA) receptor subunit subtype gene GABRA1 rs2279020 were genotyped following the Illumina protocols. There were no significant differences in allelic or genotypic frequencies between the drug responsive and resistant patients. The polymorphisms of the above SNP loci may not be associated with drug resistance of epilepsy in the Chinese Han population.
{"title":"ABCB1, ABCC2, SCN1A, SCN2A, GABRA1 gene polymorphisms and drug resistant epilepsy in the Chinese Han population.","authors":"Luo Zhou, Yuze Cao, H. Long, Lili Long, Lin Xu, Zhaoqian Liu, Ying Zhang, B. Xiao","doi":"10.1691/PH.2015.4849","DOIUrl":"https://doi.org/10.1691/PH.2015.4849","url":null,"abstract":"Drug resistance is common in epilepsy despite multiple available medications. Single nucleotide polymorphisms (SNP) may influence drug efficacy in epilepsy. We therefore aimed to clarify the association between polymorphisms of several controversial SNP loci and drug resistance in Chinese Han epilepsy patients from central China. Among all the 391 recruited subjects, 235 and 156 patients were classified into a drug responsive and resistant group, respectively, according to the definition of drug resistance proposed by the International League Against Epilepsy. The candidate SNP loci, including ATP-binding cassette (ABC) subfamily gene ABCB1 rs2032582 and rs1045642; ABC subfamily gene ABCC2 rs717620 and rs2273697; sodium channel subunit gene SCN1A rs3812718, SCN2A rs2304016; γ-amino butyric acid type A (GABAA) receptor subunit subtype gene GABRA1 rs2279020 were genotyped following the Illumina protocols. There were no significant differences in allelic or genotypic frequencies between the drug responsive and resistant patients. The polymorphisms of the above SNP loci may not be associated with drug resistance of epilepsy in the Chinese Han population.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"87 1","pages":"416-20"},"PeriodicalIF":0.0,"publicationDate":"2015-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72728197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K. Schmitz, R. Lenssen, M. Rosentreter, D. Gross, A. Eisert
In medicine today, future doctors are expected to ensure patient safety. Yet medical students often feel uncertain if they can meet these high expectations. This study aims to quantify the perceptions of medical students regarding the actual quality of their education in the fields of patient safety and, in particular, medication safety. A questionnaire was designed and distributed to about 100 upper-level medical students. The students had to respond to 12 questions regarding the following categories: 1) familiarity with patient safety and/or medication safety; 2) personal experience in high-risk clinical situations; and 3) perceived relevance of knowledge in the area of patient and medication Safety for clinical practice. Of the respondents 42.1% and 36.8% had delved into the topic patient safety and medication safety, respectively. In clinical practice 88.2% of respondents had experienced a high-risk situation for patients. Regarding patient safety and medication safety, respectively, 82.9% and 85.3% of the respondents found these topics to be particularly relevant to their clinical practice. This study has shown that there is a measurable discrepancy between the students' perceived quality of their medical education and their feelings that they are well prepared to cope with severe clinical challenges.
{"title":"Wide cleft between theory and practice: medical students' perception of their education in patient and medication safety.","authors":"K. Schmitz, R. Lenssen, M. Rosentreter, D. Gross, A. Eisert","doi":"10.1691/PH.2015.4836","DOIUrl":"https://doi.org/10.1691/PH.2015.4836","url":null,"abstract":"In medicine today, future doctors are expected to ensure patient safety. Yet medical students often feel uncertain if they can meet these high expectations. This study aims to quantify the perceptions of medical students regarding the actual quality of their education in the fields of patient safety and, in particular, medication safety. A questionnaire was designed and distributed to about 100 upper-level medical students. The students had to respond to 12 questions regarding the following categories: 1) familiarity with patient safety and/or medication safety; 2) personal experience in high-risk clinical situations; and 3) perceived relevance of knowledge in the area of patient and medication Safety for clinical practice. Of the respondents 42.1% and 36.8% had delved into the topic patient safety and medication safety, respectively. In clinical practice 88.2% of respondents had experienced a high-risk situation for patients. Regarding patient safety and medication safety, respectively, 82.9% and 85.3% of the respondents found these topics to be particularly relevant to their clinical practice. This study has shown that there is a measurable discrepancy between the students' perceived quality of their medical education and their feelings that they are well prepared to cope with severe clinical challenges.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"54 1","pages":"351-4"},"PeriodicalIF":0.0,"publicationDate":"2015-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78657398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
P. Fehér, Z. Ujhelyi, M. Vecsernyés, F. Fenyvesi, G. Damache, A. Ardelean, M. Costache, A. Dinischiotu, A. Hermenean, I. Bácskay
The main purpose of this study was to certify the effect of native silymarin oil (SM-oil) formulated in a self-microemulsifying drug delivery system (SMEDDS). The optimal formulation was 25% of SM-oil, 33.3 % of Cremophor RH40, 20% of Transcutol HP, 16.6% of Labrasol and 5% of Capryol 90. In this novel formulation the SM-oil was the active substance and the lipid part. The in vivo study examined the preventive effects of SMEDDS containing SM native seeds oil against carbon tetrachloride (CC14) induced hepatotoxicity in mice. Determination of alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels and also liver histology investigations have been done. The liver antioxidant status was determined with the concentrations of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GR), and glutathione (GSH) hepatic lipid peroxidation was examined and expressed in terms of malondialdehyde (MDA) content. The plasma levels of AST and ALT significantly diminished by pre-treatment with 500 mg/kg and 1000 mg/kg SMEDDS. The pre-treatment with 500 mg/kg and 1000 mg/kg SMEDDS increased GSH level by about 6% respectively 24% compared to the CC14 group. Due to preventive administration of 500 mg/kg and 1000 mg/kg of SMEDDS in the intoxicated animals, MDA levels were reduced by 22% respectively 58%. Also, an insignificant rise by almost 17% and 19% in the animals treated with the both doses of SMEDDS could be noticed. It can be concluded that hepatotoxicity may be avoided by the oral application of our formulation.
{"title":"Hepatoprotective effects of a self-micro emulsifying drug delivery system containing Silybum marianum native seed oil against experimentally induced liver injury.","authors":"P. Fehér, Z. Ujhelyi, M. Vecsernyés, F. Fenyvesi, G. Damache, A. Ardelean, M. Costache, A. Dinischiotu, A. Hermenean, I. Bácskay","doi":"10.1691/PH.2015.4146","DOIUrl":"https://doi.org/10.1691/PH.2015.4146","url":null,"abstract":"The main purpose of this study was to certify the effect of native silymarin oil (SM-oil) formulated in a self-microemulsifying drug delivery system (SMEDDS). The optimal formulation was 25% of SM-oil, 33.3 % of Cremophor RH40, 20% of Transcutol HP, 16.6% of Labrasol and 5% of Capryol 90. In this novel formulation the SM-oil was the active substance and the lipid part. The in vivo study examined the preventive effects of SMEDDS containing SM native seeds oil against carbon tetrachloride (CC14) induced hepatotoxicity in mice. Determination of alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels and also liver histology investigations have been done. The liver antioxidant status was determined with the concentrations of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GR), and glutathione (GSH) hepatic lipid peroxidation was examined and expressed in terms of malondialdehyde (MDA) content. The plasma levels of AST and ALT significantly diminished by pre-treatment with 500 mg/kg and 1000 mg/kg SMEDDS. The pre-treatment with 500 mg/kg and 1000 mg/kg SMEDDS increased GSH level by about 6% respectively 24% compared to the CC14 group. Due to preventive administration of 500 mg/kg and 1000 mg/kg of SMEDDS in the intoxicated animals, MDA levels were reduced by 22% respectively 58%. Also, an insignificant rise by almost 17% and 19% in the animals treated with the both doses of SMEDDS could be noticed. It can be concluded that hepatotoxicity may be avoided by the oral application of our formulation.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"1 1","pages":"231-8"},"PeriodicalIF":0.0,"publicationDate":"2015-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89542694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cerebellar Purkinje cells (PCs) respond to sensory stimulation via climbing fiber and mossy fiber-granule cell pathways, and generate motor-related outputs according to internal rules of integration and computation. However, the dynamic properties of sensory information processed by PC in mouse cerebellar cortex are currently unclear. In the present study, we examined the effects of the gamma-aminobutyric acid receptor A (GABA(A)) antagonist, gabazine, on the stimulation train on the simple spike firing of PCs by electrophysiological recordings method. Our data showed that the output of cerebellar PCs could be significantly affected by all pulses of the low-frequency (0.25 -2 Hz) sensory stimulation train, but only by the 1st and 2nd pulses of the high-frequency (≥ 4 Hz) sensory stimulation train. In the presence of gabazine (20 μM), each pulse of 1 Hz facial stimulation evoked simple spike firing in the PCs, but only the 1st and 2nd pulses of 4 Hz stimulation induced an increase in simple spike firing of the PCs. These results indicated that GABAA receptor-mediated inhibition did not significantly affect the frequency properties of sensory stimulation evoked responses in the mouse cerebellar PCs.
{"title":"Effect of gabazine on sensory stimulation train evoked response in mouse cerebellar Purkinje cells.","authors":"Yan-Hua Bing, Wenzhe Jin, L. Sun, C. Chu, D. Qiu","doi":"10.1691/PH.2015.4769","DOIUrl":"https://doi.org/10.1691/PH.2015.4769","url":null,"abstract":"Cerebellar Purkinje cells (PCs) respond to sensory stimulation via climbing fiber and mossy fiber-granule cell pathways, and generate motor-related outputs according to internal rules of integration and computation. However, the dynamic properties of sensory information processed by PC in mouse cerebellar cortex are currently unclear. In the present study, we examined the effects of the gamma-aminobutyric acid receptor A (GABA(A)) antagonist, gabazine, on the stimulation train on the simple spike firing of PCs by electrophysiological recordings method. Our data showed that the output of cerebellar PCs could be significantly affected by all pulses of the low-frequency (0.25 -2 Hz) sensory stimulation train, but only by the 1st and 2nd pulses of the high-frequency (≥ 4 Hz) sensory stimulation train. In the presence of gabazine (20 μM), each pulse of 1 Hz facial stimulation evoked simple spike firing in the PCs, but only the 1st and 2nd pulses of 4 Hz stimulation induced an increase in simple spike firing of the PCs. These results indicated that GABAA receptor-mediated inhibition did not significantly affect the frequency properties of sensory stimulation evoked responses in the mouse cerebellar PCs.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"12 1","pages":"129-34"},"PeriodicalIF":0.0,"publicationDate":"2015-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74923191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Metformin is usually used for the treatment of type 2 diabetes. Recently, many studies suggest that metformin and vitamin D have broad-spectrum antitumor activities. Our aim in this research was to study the effects of vitamin D3 combined with metformin on the apoptosis induction and its mechanisms in the human breast cancer cell line MDA-MB-231. Cell proliferation was measured by methylthiazol tetrazolium (MTT) assay. The morphology of cell apoptosis was observed after Hoechst 33342 staining. Here we show that vitamin D3 280 μg/ml or vitamin D3 300 μg/ml or vitamin D3 320 μg/ml seperately combined with metformin 15000 μg/ml exhibited synergistic effects on cell proliferation and apoptosis. The underlying anti-tumor mechanisms may involve m-TOR related pathways, which are related to activating expression of cleaved caspase-3, Bax and p-AMPK, as well as inhibiting expressions of p-Bcl-2, c-Myc, p-IGF-IR, p-mTOR, p-P70S6K, p-S6.
{"title":"Synergistic antitumor activity of vitamin D3 combined with metformin in human breast carcinoma MDA-MB-231 cells involves m-TOR related signaling pathways.","authors":"Li-Shu Guo, Hong-xia Li, Chun-Yang Li, Shengyan Zhang, Jia Chen, Qi-long Wang, Jing-Miao Gao, Jia-Qi Liang, M. Gao, Yong-jie Wu","doi":"10.1691/PH.2015.4535","DOIUrl":"https://doi.org/10.1691/PH.2015.4535","url":null,"abstract":"Metformin is usually used for the treatment of type 2 diabetes. Recently, many studies suggest that metformin and vitamin D have broad-spectrum antitumor activities. Our aim in this research was to study the effects of vitamin D3 combined with metformin on the apoptosis induction and its mechanisms in the human breast cancer cell line MDA-MB-231. Cell proliferation was measured by methylthiazol tetrazolium (MTT) assay. The morphology of cell apoptosis was observed after Hoechst 33342 staining. Here we show that vitamin D3 280 μg/ml or vitamin D3 300 μg/ml or vitamin D3 320 μg/ml seperately combined with metformin 15000 μg/ml exhibited synergistic effects on cell proliferation and apoptosis. The underlying anti-tumor mechanisms may involve m-TOR related pathways, which are related to activating expression of cleaved caspase-3, Bax and p-AMPK, as well as inhibiting expressions of p-Bcl-2, c-Myc, p-IGF-IR, p-mTOR, p-P70S6K, p-S6.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"19 1","pages":"117-22"},"PeriodicalIF":0.0,"publicationDate":"2015-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86909645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
As an inheritor of the rich medico-pharmaceutical heritage in Asia Minor, Turkey constituted a critical junction of exchange and dissemination of pharmacy knowledge between East and West throughout history. This greatly contributed to the rapid development of pharmacy as an established profession. The 20th century saw scholarly examination of the field's history: the first book on the history of pharmacy appeared in Turkish (1911); a history of pharmacy course was offered for the first time in the pharmacy curriculum (1945); the first history of pharmacy museum was founded (1960); and national conferences on the history of pharmacy were launched (1990). In addition to providing information on the milestones of the history of pharmacy studies in Turkey in the last hundred years, this study aims to statistically evaluate the change in the number of history of pharmacy-related publications per decade as well as discuss the current situation of history of pharmacy education at Turkish universities. The history of pharmacy has become a stronger and more independent academic discipline in Turkey, particularly in the last two decades. As of 2014, history of pharmacy undergraduate courses are taught at all faculties of pharmacy in Turkey, except the Yuzuncu Yil University (Van), mainly between first and fourth semesters.
{"title":"One hundred years of the history of pharmacy studies in Turkey.","authors":"H. Tekiner","doi":"10.1691/ph.2015.4096","DOIUrl":"https://doi.org/10.1691/ph.2015.4096","url":null,"abstract":"As an inheritor of the rich medico-pharmaceutical heritage in Asia Minor, Turkey constituted a critical junction of exchange and dissemination of pharmacy knowledge between East and West throughout history. This greatly contributed to the rapid development of pharmacy as an established profession. The 20th century saw scholarly examination of the field's history: the first book on the history of pharmacy appeared in Turkish (1911); a history of pharmacy course was offered for the first time in the pharmacy curriculum (1945); the first history of pharmacy museum was founded (1960); and national conferences on the history of pharmacy were launched (1990). In addition to providing information on the milestones of the history of pharmacy studies in Turkey in the last hundred years, this study aims to statistically evaluate the change in the number of history of pharmacy-related publications per decade as well as discuss the current situation of history of pharmacy education at Turkish universities. The history of pharmacy has become a stronger and more independent academic discipline in Turkey, particularly in the last two decades. As of 2014, history of pharmacy undergraduate courses are taught at all faculties of pharmacy in Turkey, except the Yuzuncu Yil University (Van), mainly between first and fourth semesters.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"68 1","pages":"139-44"},"PeriodicalIF":0.0,"publicationDate":"2015-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90702864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OBJECTIVE To study the effects of vitamin D3 combined with metformin on the proliferation and apoptosis in human bladder cancer cell line SW-780 and its possible mechanism. METHODS MTT assay and fluorescence microscope observations were used to study the effects of vitamin D3 combined with metformin on the proliferation and apoptosis of SW-780 cells in vitro. Western blot was used to detect the expression of apoptosis-related proteins p-Bcl-2, Bax, Cyclin D1, c-Myc and related signaling pathways activated proteins p-IGF-IR, p-mTOR, p-P70S6K, p-S6. RESULTS MTT results showed that 320 μg/ml vitamin D3 combined with 620 μg/ml metformin acting on cells for 48h had a significant synergistic effect on proliferation. Fluorescence microscope observations showed that compared with negative control group and monotherapy treatment group, the apoptosis features of combination treatment group were obvious and the apoptosis rate increased greatly. Western blot showed that compared with the negative control group and monotherapy treatment group, the expression levels of p-Bcl-2, Cyclin D1 and c-Myc in combination treatment group significantly decreased, whereas the expression level of Bax significantly increased, and the expression levels of p-IGF-IR, p-mTOR, p-P70S6K and p-S6 in combination treatment group significantly decreased. CONCLUSION Vitamin D3 combined with metformin exhibited obvious inhibitory effects on the cell proliferation and apoptosis induction in SW-780 cells. The underlying anti-tumor mechanism might be related to inhibiting the expressions of p-Bcl-2, Cyclin D1, c-Myc, p-IGF-IR, p-mTOR, p-P70S6K, p-S6 and activating the expression of Bax.
{"title":"Vitamin D3 enhances antitumor activity of metformin in human bladder carcinoma SW-780 cells.","authors":"Li-Shu Guo, Hong-xia Li, Chun-Yang Li, Shengyan Zhang, Jia Chen, Qi-long Wang, Jing-Miao Gao, Jia-Qi Liang, M. Gao, Yong-jie Wu","doi":"10.1691/PH.2015.3936","DOIUrl":"https://doi.org/10.1691/PH.2015.3936","url":null,"abstract":"OBJECTIVE\u0000To study the effects of vitamin D3 combined with metformin on the proliferation and apoptosis in human bladder cancer cell line SW-780 and its possible mechanism.\u0000\u0000\u0000METHODS\u0000MTT assay and fluorescence microscope observations were used to study the effects of vitamin D3 combined with metformin on the proliferation and apoptosis of SW-780 cells in vitro. Western blot was used to detect the expression of apoptosis-related proteins p-Bcl-2, Bax, Cyclin D1, c-Myc and related signaling pathways activated proteins p-IGF-IR, p-mTOR, p-P70S6K, p-S6.\u0000\u0000\u0000RESULTS\u0000MTT results showed that 320 μg/ml vitamin D3 combined with 620 μg/ml metformin acting on cells for 48h had a significant synergistic effect on proliferation. Fluorescence microscope observations showed that compared with negative control group and monotherapy treatment group, the apoptosis features of combination treatment group were obvious and the apoptosis rate increased greatly. Western blot showed that compared with the negative control group and monotherapy treatment group, the expression levels of p-Bcl-2, Cyclin D1 and c-Myc in combination treatment group significantly decreased, whereas the expression level of Bax significantly increased, and the expression levels of p-IGF-IR, p-mTOR, p-P70S6K and p-S6 in combination treatment group significantly decreased.\u0000\u0000\u0000CONCLUSION\u0000Vitamin D3 combined with metformin exhibited obvious inhibitory effects on the cell proliferation and apoptosis induction in SW-780 cells. The underlying anti-tumor mechanism might be related to inhibiting the expressions of p-Bcl-2, Cyclin D1, c-Myc, p-IGF-IR, p-mTOR, p-P70S6K, p-S6 and activating the expression of Bax.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"18 1","pages":"123-8"},"PeriodicalIF":0.0,"publicationDate":"2015-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77875404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
H. Gong, Huan Li, M. Yan, Bi-kui Zhang, P. Jiang, Xin-Rong Fan, Yang Deng
Licorice has a marked detoxifying effect that can treat drug poisoning and/or relieve adverse effects. However, the exact mechanism of this action is not entirely elucidated, but is believed to be related to the modulation of drug disposition when interacting with other drugs. Additionally, Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a significant role in mediating phase II xenobiotic metabolizing enzymes (XMEs) and phase III transporters. In the present study, we showed that licorice induced the mRNA expression of phase II XMEs UDP-glucuronosyltransferases 1A1 (UGT1A1), glutamate cysteine ligase (GCL), glutathione-s-transferase (GST) and phase III transporters multidrug resistance protein 2 (MRP2), as well as a rapid increase in Nrf2 nuclear accumulation. These findings suggests that licorice may intervene in the Nrf2 signal pathway to induce UGT1A1, GCLC, GST and MRP2, which provide a novel mechanism for the use of licorice to treat drug poisoning and/or relieve adverse effects.
{"title":"Effect of licorice on the induction of phase II metabolizing enzymes and phase III transporters and its possible mechanism.","authors":"H. Gong, Huan Li, M. Yan, Bi-kui Zhang, P. Jiang, Xin-Rong Fan, Yang Deng","doi":"10.1691/PH.2014.4615","DOIUrl":"https://doi.org/10.1691/PH.2014.4615","url":null,"abstract":"Licorice has a marked detoxifying effect that can treat drug poisoning and/or relieve adverse effects. However, the exact mechanism of this action is not entirely elucidated, but is believed to be related to the modulation of drug disposition when interacting with other drugs. Additionally, Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a significant role in mediating phase II xenobiotic metabolizing enzymes (XMEs) and phase III transporters. In the present study, we showed that licorice induced the mRNA expression of phase II XMEs UDP-glucuronosyltransferases 1A1 (UGT1A1), glutamate cysteine ligase (GCL), glutathione-s-transferase (GST) and phase III transporters multidrug resistance protein 2 (MRP2), as well as a rapid increase in Nrf2 nuclear accumulation. These findings suggests that licorice may intervene in the Nrf2 signal pathway to induce UGT1A1, GCLC, GST and MRP2, which provide a novel mechanism for the use of licorice to treat drug poisoning and/or relieve adverse effects.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"10 1","pages":"894-7"},"PeriodicalIF":0.0,"publicationDate":"2014-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85965564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Previous studies suggest that B-type natriuretic peptide (BNP) exerts inhibitory effects on cardiac hypertrophy. Our studies have shown that long-term treatment of rats with BNP attenuated cardiac hypertrophy via down-regulation of TGF-β1 and up-regulation of smad7. However, the mechanisms have not been fully elucidated. In the present study, we examined the role of endogenous BNP on cardiomyocyte hypertrophy and the related molecular mechanisms. Cardiomyocytes from neonatal rats were cultured and a cardiomyocyte hypertrophy model was established with angiotensin II (Ang II). The effects of blockade of endogenous BNP by its receptor antagonist, HS-142-1, on cell hypertrophy were investigated. Cardiomyocyte hypertrophy indices, including cell surface area, protein content and [3H] incorporation were measured. Smad and mitogen-activated protein kinase (MAPK) protein expressions were detected using Western blot analysis. We found that HS-142-1 increased Ang II-stimulated cardiomyocyte hypertrophy and Smad activation. In addition, the increase of cardiomyocyte hypertrophy and the activation of Smad caused by HS-142-1 were not altered by the ERK inhibitor, PD98059, but were decreased by the p38 MAPK inhibitor, SB203580. These results demonstrate that endogenous BNP attenuates cardiomyocyte hypertrophy, and this may be mediated through p38 MAPK/Smad, but not ERK/Smad signaling pathway.
{"title":"Endogenous BNP attenuates cardiomyocyte hypertrophy induced by Ang II via p38 MAPK/Smad signaling.","authors":"Yili Chen, Fengjuan Yao, Shenglong Chen, Huiling Huang, Lingling Wu, Jiangui He, Yugang Dong","doi":"10.1691/PH.2014.4610","DOIUrl":"https://doi.org/10.1691/PH.2014.4610","url":null,"abstract":"Previous studies suggest that B-type natriuretic peptide (BNP) exerts inhibitory effects on cardiac hypertrophy. Our studies have shown that long-term treatment of rats with BNP attenuated cardiac hypertrophy via down-regulation of TGF-β1 and up-regulation of smad7. However, the mechanisms have not been fully elucidated. In the present study, we examined the role of endogenous BNP on cardiomyocyte hypertrophy and the related molecular mechanisms. Cardiomyocytes from neonatal rats were cultured and a cardiomyocyte hypertrophy model was established with angiotensin II (Ang II). The effects of blockade of endogenous BNP by its receptor antagonist, HS-142-1, on cell hypertrophy were investigated. Cardiomyocyte hypertrophy indices, including cell surface area, protein content and [3H] incorporation were measured. Smad and mitogen-activated protein kinase (MAPK) protein expressions were detected using Western blot analysis. We found that HS-142-1 increased Ang II-stimulated cardiomyocyte hypertrophy and Smad activation. In addition, the increase of cardiomyocyte hypertrophy and the activation of Smad caused by HS-142-1 were not altered by the ERK inhibitor, PD98059, but were decreased by the p38 MAPK inhibitor, SB203580. These results demonstrate that endogenous BNP attenuates cardiomyocyte hypertrophy, and this may be mediated through p38 MAPK/Smad, but not ERK/Smad signaling pathway.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"69 11 1","pages":"833-7"},"PeriodicalIF":0.0,"publicationDate":"2014-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78737313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lipophilicity, expressed by log P, is an important physicochemical property of drugs that affects many biological processes, including drug absorption and distribution. The main purpose of this study to determine the log P values of newly discovered drug leads using reversed-phase high-performance liquid chromatography (RP-HPLC). The reference standards, with varying polarity ranges, were dissolved in methanol and analyzed by RP-HPLC using a C18 column. The mobile phase consisted of a mixture of acetonitrile, methanol and water in a gradient elution mode. A calibration curve was plotted between the experimental log P values and obtained log k values of the reference standard compounds and a best fit line was obtained. The log k values of the new drug leads were determined in the same solvent system and were used to calculate the respective log P values by using the best fit equation. The log P vs. log k data gave a best fit linear curve that had an R2 of 0.9786 with Pvalues of the intercept and slope of 1.19 x 10(-6) and 1.56 x 10(-10), respectively, at 0.05 level of significance. Log P values of 15 new drug leads and related compounds, all of which are derivatives of macrocyclic polyamines and their metal complexes, were determined. The values obtained are closely related to the calculated log P (Clog P) values using ChemDraw Ultra 12.0. This experiment provided efficient, fast and reasonable estimates of log P values of the new drug leads by using RP-HPLC.
以log P表示的亲脂性是影响药物吸收和分布等许多生物过程的重要理化性质。本研究的主要目的是利用反相高效液相色谱法(RP-HPLC)测定新发现药物先导物的对数P值。将不同极性范围的标准品溶于甲醇中，采用C18色谱柱进行反相高效液相色谱分析。流动相由乙腈、甲醇和水的混合物组成，采用梯度洗脱模式。在标准化合物的实验对数P值与得到的对数k值之间绘制校准曲线，得到最佳拟合线。在同一溶剂体系中测定新药先导物的log k值，并利用最佳拟合方程计算各自的log P值。log P与log k数据的最佳拟合线性曲线R2为0.9786，截距和斜率的P值分别为1.19 x 10(-6)和1.56 x 10(-10)，显著性水平为0.05。测定了15种新药物先导物及其相关化合物的Log P值，它们均为大环多胺及其金属配合物的衍生物。所得值与使用ChemDraw Ultra 12.0计算的log P (Clog P)值密切相关。本实验采用反相高效液相色谱法对新药先导物的log P值进行了高效、快速、合理的估计。
{"title":"Determination of log P values of new cyclen based antimalarial drug leads using RP-HPLC.","authors":"A. Rudraraju, P. Amoyaw, T. Hubin, M. O. Khan","doi":"10.1691/PH.2014.4019","DOIUrl":"https://doi.org/10.1691/PH.2014.4019","url":null,"abstract":"Lipophilicity, expressed by log P, is an important physicochemical property of drugs that affects many biological processes, including drug absorption and distribution. The main purpose of this study to determine the log P values of newly discovered drug leads using reversed-phase high-performance liquid chromatography (RP-HPLC). The reference standards, with varying polarity ranges, were dissolved in methanol and analyzed by RP-HPLC using a C18 column. The mobile phase consisted of a mixture of acetonitrile, methanol and water in a gradient elution mode. A calibration curve was plotted between the experimental log P values and obtained log k values of the reference standard compounds and a best fit line was obtained. The log k values of the new drug leads were determined in the same solvent system and were used to calculate the respective log P values by using the best fit equation. The log P vs. log k data gave a best fit linear curve that had an R2 of 0.9786 with Pvalues of the intercept and slope of 1.19 x 10(-6) and 1.56 x 10(-10), respectively, at 0.05 level of significance. Log P values of 15 new drug leads and related compounds, all of which are derivatives of macrocyclic polyamines and their metal complexes, were determined. The values obtained are closely related to the calculated log P (Clog P) values using ChemDraw Ultra 12.0. This experiment provided efficient, fast and reasonable estimates of log P values of the new drug leads by using RP-HPLC.","PeriodicalId":86039,"journal":{"name":"Die Pharmazie. Beihefte","volume":"20 1","pages":"655-62"},"PeriodicalIF":0.0,"publicationDate":"2014-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88339953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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